The increased incidence of birth defects and fetal deaths associated with such complications of pregnancy as pre-eclamptic toxemia, diabetes mellitus and rhesus incompatibility makes an understanding of the placental abormalities which occur in these conditions of major importance. The human placenta selectively supplies the fetus with oxygen and nutrients necessary for its survival and normal development. The villar basement membrane is a key element in this selective permeability barrier and any change in its structure could affect its normal function and have adverse consequences on the development of the fetus. Very little is known about the composition and structure of the normal placental basement membrane and almost nothing of the abnormal membrane. The overall aim of this research project is to investigate the nature and structural basis of the basement membrane alterations in the human placenta in abnormal human pregnancies. The main questions to be answered are the following: 1. Are there differences in the amino acid and carbohydrate composition of placental basement membranes from mothers with normal and abnormal human pregnancies? 2. Are there qualitative and quantitative changes in the glycoprotein and collagenous components of placental basement membranes in abnormal pregnancies? 3. Is the crosslinking of the basement membrane altered in placentas from mothers with complications of pregnancy related to placental permeability changes? 4. Is there a correlation between the degree and nature of alteration in placental basement membrane morphology and the composition and structure of the basement membrane? The answers to these questions will be sought by the isolation, analysis and fractionation of basement membranes from placentas of mothers with normal and complicated pregnancies.